Nobel Winner Is Caught Up In a Dispute Over Study

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Seventeen pages of private laboratory notes that fell into the hands of an obscure junior scientist have set off a bitter dispute over the accuracy of a scientific paper whose authors included a Nobel Prize winner, Dr. David Baltimore of the Massachusetts Institute of Technology.

At issue is whether the notes support or contradict a central finding of the paper, written by a team of six scientists and published in the journal Cell on April 25, 1986.

The dispute calls into question a dramatic conclusion in the paper about genetic control of the immune system that has been challenged on other grounds as well. It also provides a rare glimpse into the workings of a renowned scientific team and into what happens behind the scenes when charges are made that threaten to tarnish reputations.

Among the troubling issues raised are whether junior scientists can challenge their seniors without harming their own reputations, who should have access to laboratory data behind published papers, whether scientific institutions can be trusted to police themselves for error, and whether the policing can itself inhibit scientific daring.

The dispute is entering the political arena this week as some key figures testify before two Congressional committees.

The charges and countercharges will also be evaluated by a panel now being assembled by the National Institutes of Health that, officials hope, will provide a persuasive judgment on the case, which has left many observers thoroughly confused.

The scientific paper was important chiefly because it described a wholly unexpected result with important implications for the immune system. As reported, the experiments found that when foreign genes were introduced into a mouse, the mouse's own genes were somehow influenced, causing them to produce proteins closely related to those that the foreign gene produces. This kind of influence of one type of gene on another had not previously been seen. But, if the critics are right, it was not seen in this experiment either.

Standing on one side of the dispute are Dr. Margot O'Toole, a former postdoctoral research fellow at M.I.T., who concluded that the results in the disputed paper were not in accord with 17 pages of records that came into her hands while she was working in a laboratory involved in the study. Her view is supported by at least one other junior scientist of the same laboratory, who reached the same conclusion independently, and by two Government scientists who have made an exhaustive comparison of the paper and the laboratory notes, Walter W. Stewart and Dr. Ned Feder of the National Institutes of Health.

Mr. Stewart and Dr. Feder, who have become regular critics of misconduct in science, contend that the laboratory records ''flatly contradict'' key results in the paper and have called for a public correction. They charge that the paper was ''grossly misleading'' because it misrepresented the laboratory data on which its conclusions were based. They insist that they are not alleging fraud or wrongdoing, but charge at a minimum that the papers' authors are stubbornly refusing to correct serious defects in the report.

On the other side of the dispute are Dr. Baltimore, who did not himself perform the challenged research but who has acted as the chief spokesman for the team, and Dr. Thereza Imanishi-Kari, who conducted the disputed research while she was at M.I.T. but has since joined the Tufts University School of Medicine in Boston.

The fracas has already exacted a shattering toll on the two scientists most centrally involved. Dr. O'Toole, the accuser, has been branded a ''discontented'' post-doctoral fellow by Dr. Baltimore and her competence has been criticized by Dr. Imanishi-Kari. She believes her career has been seriously harmed or even ''destroyed.''

Dr. Imanishi-Kari, the accused, said in an interview that the dispute ''has destroyed my private life completely'' by undermining her ability to be a role model for her child. ''Psychologically, this has been terrible, absolutely terrible,'' she said. ''It's the worst thing that could happen to a scientist - an accusation of mishandling data.''

Dr. Baltimore said in an interview and a prepared statement that the paper had produced ''surprising findings'' and ''charted new ground.'' He called the paper ''very arcane'' and said it could be understood only by experts in the field. He said the allegations against his team had already been reviewed ''by eminent immunologists at M.I.T. and Tufts University and were found to be groundless.'' In both cases., he said, ''the reviews affirmed the interpretation of the data.'' 'Judge and Jury'

Noting that as part of those reviews his team had shown all its data to qualified experts, Dr. Baltimore said he saw no reason now to share more of the background data with Mr. Stewart and Dr. Feder just because they had ''decided to become judge and jury.''

The Tufts review, led by Dr. Henry Wortis, found that there was no evidence of deliberate falsification or misrepresentation and that, while alternative explanations of the underlying data could be made, ''that is the stuff of science.'' Dr. Wortis acknowledged that all three members of his review panel had ''scientific and friendly relations with Dr. Imanishi-Kari,'' whose work they were investigating. But he said he also had ties to Dr. O'Toole, having taught both her and her husband.

The M.I.T. review, headed by Dr. Herman N. Eisen, acknowledged that Dr. O'Toole had found at least one error in the paper. But Dr. Eisen concluded it was ''not a flagrant error'' and was ''too minor'' to rate either a letter of correction or a complete retraction of the original paper.

Other respected scientists who are not parties to the controversy believe the disputed paper was indeed wrong. Dr. Leonore A. Herzenberg and Dr. Leonard A. Herzenberg of the Stanford University School of Medicine, who have done similar experiments and have worked with Dr. Baltimore, said in a Jan. 14 letter to Mr. Stewart and Dr. Feder that Dr. O'Toole's criticisms were ''original and creative,'' adding, ''They suggest but do not prove that an error of significant proportions was made.''

They said their own recent studies ''demonstrate directly that the original study must have been faulty in some way.'' But the Herzenbergs opposed the attempts to force a ''public airing'' of the matter.

Dr. Howard Temin of the University of Wisconsin, who shared the 1975 Nobel Prize in Physiology or Medicine with Dr. Baltimore, said, ''It does appear that the paper was in error.' A Skeptic in the Lab

Although no one has publicly accused Dr. Imanishi-Kari of either fraud or misconduct, that was clearly one possible implication of the charge that her laboratory records contradicted what she published. ''I should stress that I do not believe that any misconduct took place in the laboratory of Dr. Imanishi-Kari or by anyone involved in this research,'' Dr. Baltimore said in his statement. ''She is a capable scientist, and others who have reviewed this research agree with her methods and findings.''

Dr. Imanishi-Kari charged that Mr. Stewart and Dr. Feder ''are not even immunologists'' and ''don't understand how the tests were done.'' She called it ''completely unethical'' and ''absolutely outrageous'' for them to obtain and criticize a portion of her laboratory records.

A graduate student in Dr. Imanishi-Kari's laboratory, Charles Maplethorpe, became skeptical of what he called ''these stupendous results'' before they were published. Dr. Maplethorpe had frequently been at odds with Dr. Imanishi-Kari and was denied access to the underlying data. One evening he took a covert peak at the records of one key test and concluded that they showed the opposite of what Dr. Imanishi-Kari had concluded.

Before leaving M.I.T. in August 1985, Dr. Maplethorpe said he conveyed his concerns to a senior biologist, who essentially told him not to worry because the scientific truth would eventually emerge, and to a key assistant to the president of M.I.T., who blanched and handed him guidelines for filing fraud charges. Dr. Maplethorpe, who was about to get his doctorate, backed away lest he be accused of vindictiveness against Dr. Imanishi-Kari, he said.

''I figured I had done my part,'' he said. ''I left the university with a feeling of disgust.''

About that time, Dr. O'Toole was beginning to work in the laboratory. She was assigned to do experiments to further elucidate the surprising findings but soon found that they would not work, leading her to question the original findings. Her repeated requests to see the underlying data were brushed aside. Criticisms Passed Along

One day, while examining the breeding records for a mouse, she stumbled onto the 17 pages of records. She photocopied them, studied them closely, and became convinced that they contradicted several major assertions in the now-published paper. In particular, she concluded that various laboratory tests were inadequate to determine whether proteins had been produced by the foreign genes or the normal genes. The data suggested to her that the foreign genes were producing proteins, while the paper asserted that they generally were not.

Dr. O'Toole took her criticisms to senior scientists at both Tufts and M.I.T. and confronted Dr. Imanishi-Kari and Dr. Baltimore with them, but she was unable to obtain the correction she sought.

In a recent interview, she criticized the ''very pervasive'' attitude that ''scientific error does not have to be corrected.''

''I believed that a correction was necessary,'' she said. ''I did this as a matter of professional responsibility. I raised substantive scientific objections and the only replies I got were ad hominen attacks. I think the system is now so competitive that it actually selects against the correction of error.'' A Critique Was Blocked

Meanwhile, Dr. Maplethorpe, who had read about Mr. Stewart and Dr. Feder and their challenging scientific misconduct, alerted them to the situation.

Mr. Stewart subsequently persuaded Dr. O'Toole to give him copies of the 17 pages of notes, and he and Dr. Feder prepared a detailed critique. Later, they also pressed for the full laboratory records but were rebuffed by Dr. Baltimore, who wrote, ''I do not recognize your right to set yourselves up as guardians of scientific purity.''

At N.I.H., publication of the Stewart-Feder critique was blocked for about seven months while efforts were made to resolve the scientific disagreement. After the American Civil Liberties Union intervened on their behalf, the Stewart-Feder manuscript was released. It has since been rejected by two prominent journals, Cell and Science, on the ground that the issue was more appropriate for an investigating committee than a scientific journal.

The N.I.H. panel investigating the case has been the subject of controversy itself. It is being reconstituted after critics cited the ties of two of the three members to Dr. Baltimore.

A version of this article appears in print on , Section C, Page 1 of the National edition with the headline: Nobel Winner Is Caught Up In a Dispute Over Study. Order Reprints | Today’s Paper | Subscribe